1,721,002 research outputs found
Hepatocellular carcinoma and lifestyles.
No full textThe majority of hepatocellular carcinoma occurs over pre-existing chronic liver diseases that share cirrhosis as an endpoint. In the last decade, a strong association between lifestyle and hepatocellular carcinoma has become evident. Abundance of energy-rich food and sedentary lifestyles have caused metabolic conditions such as obesity and diabetes mellitus to become global epidemics. Obesity and diabetes mellitus are both tightly linked to non-alcoholic fatty liver disease and also increase hepatocellular carcinoma risk independent of cirrhosis. Emerging data suggest that physical activity not only counteracts obesity, diabetes mellitus and non-alcoholic fatty liver disease, but also reduces cancer risk. Physical activity exerts significant anticancer effects in the absence of metabolic disorders. Here, we present a systematic review on lifestyles and hepatocellular carcinoma
Genomic Analysis of Early Hereditary Diffuse Gastric Cancer
No full textDiffuse gastric cancer (DGC) is one of the two main types of stomach cancer. Histologically, DGC can be subdivided into poorly differentiated carcinoma and signet ring cell carcinoma (SRCC). Carriers of germline mutations in the gene encoding E-cadherin (CDH1) are predisposed to DGC (hereditary DGC, HDGC). Essentially all asymptomatic mutation carriers present with occult, multifocal SRCC confined to the gastric mucosa before they develop advanced disease. Initial characterisation of these early HDGC foci (referred to as eHDGC) suggests an indolent nature of these lesions, contrary to their current pathological definition as malignant disease.
The main aim of this study was to determine if genomic instability is an early event in HDGC and how it might lead to disease progression. We assessed chromosomal aberrations in the early intramucosal eHDGCs by using array comparative genomic hybridisation (CGH). Taking advantage of possibly the largest eHDGC collection worldwide, we analysed tissue from twelve members of one HDGC family, all carrying the same CDH1 mutation. All specimens were formalin-fixed paraffin-embedded (FFPE), as eHDGC is generally identified in resected stomachs by microscopy due to both its intramucosal location and the small size of the foci. As a result, the first part of this study focussed on the optimisation and establishment of techniques for the genomic analysis of degraded DNA from minimal amounts of laser-capture microdissected (LCM) neoplastic cells.
In the first step, we assessed several histological stains for their suitability in identifying neoplastic cells found in eHDGCs, followed by an optimisation of the LCM procedure to obtain consistent dissection of individual cells. Next, we evaluated different DNA extraction parameters to obtain sufficient amounts of DNA for genomic profiling and established a multiplex PCR reaction as a quality control for the prediction of successful profiling. Since no agreement exists on the most suitable platform for the profiling of FFPE-DNA, two different array CGH systems were compared. DNA from FFPE and matched fresh-frozen (FF) tissue was separately analysed on both a SNP-based array (Affymetrix) and on an oligonucleotide-based array (Agilent), and resulting profiles were evaluated for the level of agreement between matched pairs of FFPE and FF samples. On the SNP-array, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the oligonucleotide array were highly concordant, indicating the reliability of this platform for the analysis of degraded DNA.
We then proceeded with the genomic analysis of the early HDGC foci. For all twelve HDGC patients, 30,000 cells from each of three tissue types, signet ring cells (SRC), poorly differentiated cells (PDCs) and non-malignant epithelial cells were dissected and analysed using the Agilent platform. Chromosomal aberrations were found in SRCs and PDCs, and confirmed by multiplex ligation dependent probe amplification (MLPA). No changes were detected that were common to all patients. Accordingly, no common genes, pathways, or miRNAs were identified to be altered in eHDGC, suggesting the aberrations had not yet undergone clonal selection. Importantly, no aneuploidy or other large-scale chromosomal rearrangements were detected. Instead, all aberrations affected small regions (< 4.8 Mb) and were predominantly deletions. Analysis of DNA sequence patterns revealed that essentially all aberrations possess the characteristics of common fragile sites. The presence of genomic instability at the fragile sites in the absence of widespread genomic instability was highly consistent with eHDGC being relatively indolent. We therefore examined by immunohistochemistry the activity of key DNA repair proteins in eHDGC. ATM-H2AX-CHK2 were consistently expressed and activated in all examined eHDGC foci, indicating an intact and activated DNA repair system accompanying genomic instability at fragile sites.
Altogether, this study has established the methodology for the successful CGH profiling of FFPE tissue and has provided the first genetic characterisation of the earliest stage of DGC development. This analysis and subsequent immunohistochemical examination has shown that early stage intramucosal DGCs are (unlike advanced DGC) typified by low levels of genomic instability at fragile sites. Moreover, they express an active DNA damage response (DDR), providing a molecular basis for the observed indolence of eHDGC
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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